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10 results on '"MESH: Plasminogen"'

1. Plasminogen gene mutation with normal C1 inhibitor hereditary angioedema: Three additional French families

Author

F. Defendi, Gaëlle Hardy, Isabelle Boccon-Gibod, Raphaël Marlu, Aude Belbézier, Chantal Dumestre Perard, Laurence Bouillet, David Launay, Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre de référence des angioedèmes à kinines (CREAK), CHU de Grenoble UF de Biochimie Génétique et Moléculaire, 38000, Grenoble, France., Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'immunologie [CHU Grenoble], CHU de Grenoble, Barrière Naturelle et Infectiosité (TIMC-IMAG-BNI), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre National de Reference des Angioedemes à Kinines, CHU Grenoble, Service de médecine interne [Lille], and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
0301 basic medicine, MESH: Mutation, MESH: Complement C1 Inhibitor Protein, Immunology, Plasminogen Gene, MESH: Angioedemas, Hereditary, C1-inhibitor, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, MESH: Plasminogen, medicine, Immunology and Allergy, Humans, ComputingMilieux_MISCELLANEOUS, Genetics, MESH: Humans, biology, business.industry, Angioedemas, Hereditary, Plasminogen, medicine.disease, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Hereditary angioedema, Mutation (genetic algorithm), Mutation, biology.protein, business, Complement C1 Inhibitor Protein
Abstract

International audience

Published
2018
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2. Cortical-layer-specific effects of PACAP and tPA on interneuron migration during post-natal development of the cerebellum

Author

Emilie Raoult, Magalie Bénard, Hitoshi Komuro, Denis Vivien, Hubert Vaudry, Alain Fournier, David Vaudry, Alexis Lebon, Ludovic Galas, Laflamme, Nancy, Plate-Forme de Recherche en Imagerie Cellulaire de Haute-Normandie (PRIMACEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-High-tech Research Infrastructures for Life Sciences (HeRacLeS), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Différenciation et communication neuronale et neuroendocrine (DC2N), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), International Associated laboratory Samuel de Champlain, Institut National de la Recherche Scientifique [Québec] (INRS)-Université de Rouen Normandie (UNIROUEN), Cleveland Clinic, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), This work was supported by the Institute for Research and Innovation in Biomedicine (IRIB), the Cell Imaging Platform of Normandy (PRIMACEN), INSERM, the FEDER (# 2517), Interreg 4A TC2N European project, the LARC-Neurosciences Network, and the Region Haute-Normandie., Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS)

Subjects
Male, Cerebellum, PACAP, Biochemistry, Tissue plasminogen activator, MESH: Plasminogen Activator Inhibitor 1, Interneuron migration, chemistry.chemical_compound, 0302 clinical medicine, Cell Movement, MESH: Tissue Plasminogen Activator, [CHIM] Chemical Sciences, MESH: Plasminogen, MESH: Animals, MESH: Cell Movement, 0303 health sciences, interneuron migration, Immunohistochemistry, MESH: Interneurons, Cell biology, [SDV.TOX] Life Sciences [q-bio]/Toxicology, medicine.anatomical_structure, Tissue Plasminogen Activator, Plasminogen activator inhibitor-1, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Pituitary Adenylate Cyclase-Activating Polypeptide, basket and stellate cells, Female, medicine.drug, Interneuron, Internal granular layer, cerebellum, MESH: Rats, MESH: Cytoplasmic Granules, Cytoplasmic Granules, Cerebellar Cortex, 03 medical and health sciences, Cellular and Molecular Neuroscience, Organ Culture Techniques, Interneurons, Plasminogen Activator Inhibitor 1, medicine, Animals, [CHIM]Chemical Sciences, tPA, Rats, Wistar, 030304 developmental biology, MESH: Cerebellar Cortex, MESH: Pituitary Adenylate Cyclase-Activating Polypeptide, granule neurons, Plasminogen, MESH: Immunohistochemistry, MESH: Rats, Wistar, MESH: Cerebellum, MESH: Male, MESH: Organ Culture Techniques, Rats, chemistry, nervous system, Hepatic stellate cell, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Neuroscience, Plasminogen activator, MESH: Female, 030217 neurology & neurosurgery
Abstract

International audience; During early post-natal development of the cerebellum, granule neurons (GN) execute a centripetal migration toward the internal granular layer, whereas basket and stellate cells (B/SC) migrate centrifugally to reach their final position in the molecular layer (ML). We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates in vitro the expression and release of the serine protease tissue-type plasminogen activator (tPA) from GN, but the coordinated role of PACAP and tPA during interneuron migration has not yet been investigated. Here, we show that endogenous PACAP is responsible for the transient arrest phase of GN at the level of the Purkinje cell layer (PCL) but has no effect on B/SC. tPA is devoid of direct effect on GN motility in vitro, although it is widely distributed along interneuron migratory routes in the ML, PCL, and internal granular layer. Interestingly, plasminogen activator inhibitor 1 reduces the migration speed of GN in the ML and PCL, and that of B/SC in the ML. Taken together, these results reveal for the first time that tPA facilitates the migration of both GN and fast B/SC at the level of their intersection in the ML through degradation of the extracellular matrix. Crucial role of tissue plasminogen activator (tPA) in interneuron migration. Interneuron migration is a critical step for normal establishment of neuronal network. This study indicates that, in the post-natal cerebellum, tPA facilitates the opposite migration of immature excitatory granule neurons (GN) and immature inhibitory basket/stellate cells (B/SC) along the same migratory route. These data show that tPA exerts a pivotal role in neurodevelopment.

Published
2014
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3. Plasminogen in cerebrospinal fluid originates from circulating blood

Author

Cyrille Orset, Sara Martinez de Lizarrondo, Alexandre Mansour, Eduardo Anglés-Cano, G. Pepe, Anna Mezzapesa, Sabrina Matà, Denis Vivien, Guglielmina Chimienti, Loïc Doeuvre, Laurent Plawinski, Dupuis, Christine, Department of Biosciences, Biotechnologies, and Biopharmaceutics, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, Università degli Studi di Firenze = University of Florence (UniFI)-Careggi Hospital, Innovations thérapeutiques en hémostase (IThEM - U1140), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), We acknowledge financial support from ADISU Puglia, Consorzio Interuniversità per le Biotecnologie, Italy, and Società Italiana di Biochimica e Biologia Molecolare for the mobility to AM., Università degli studi di Bari Aldo Moro (UNIBA), Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Inserm, Università degli studi di Bari, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de la Recherche Scientifique ( CNRS ), Università degli Studi di Firenze [Firenze], Innovations thérapeutiques en hémostase ( IThEM - U1140 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-Careggi Hospital, Chimie et Biologie des Membranes et des Nanoobjets ( CBMN ), Université Sciences et Technologies - Bordeaux 1-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux ( ENITAB ) -Centre National de la Recherche Scientifique ( CNRS ), and Careggi Hospital-University of Florence

Subjects
Male, MESH: Inflammation, Pathology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Lipopolysaccharide, MESH : Microscopy, Fluorescence, MESH: Microscopy, Fluorescence, MESH : Blotting, Western, Systemic inflammation, MESH : Blood-Brain Barrier, MESH: Blood-Brain Barrier, chemistry.chemical_compound, Cerebrospinal fluid, Blood-cerebrospinal fluid barrier, MESH: Plasminogen, MESH: Animals, MESH : Rats, General Neuroscience, 3. Good health, medicine.anatomical_structure, Neurology, MESH : Plasminogen, Blood-Brain Barrier, Immunohistochemistry, Choroid plexus, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, medicine.medical_specialty, LPS, MESH: Rats, MESH : Male, Central nervous system, Blotting, Western, Immunology, Inflammation, MESH : Rats, Wistar, Blood–cerebrospinal fluid barrier, Cellular and Molecular Neuroscience, medicine, MESH : Choroid plexus, Animals, Humans, MESH: Blotting, Western, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Rats, Wistar, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Inflammation, MESH: Humans, business.industry, Multiple sclerosis, Research, MESH : Humans, [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, Plasminogen, MESH: Choroid plexus, MESH: Rats, Wistar, medicine.disease, MESH: Male, Rats, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, chemistry, Microscopy, Fluorescence, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Animals, business
Abstract

Background Plasminogen activation is a ubiquitous source of fibrinolytic and proteolytic activity. Besides its role in prevention of thrombosis, plasminogen is involved in inflammatory reactions in the central nervous system. Plasminogen has been detected in the cerebrospinal fluid (CSF) of patients with inflammatory diseases; however, its origin remains controversial, as the blood–CSF barrier may restrict its diffusion from blood. Methods We investigated the origin of plasminogen in CSF using Alexa Fluor 488–labelled rat plasminogen injected into rats with systemic inflammation and blood–CSF barrier dysfunction provoked by lipopolysaccharide (LPS). Near-infrared fluorescence imaging and immunohistochemistry fluorescence microscopy were used to identify plasminogen in brain structures, its concentration and functionality were determined by Western blotting and a chromogenic substrate assay, respectively. In parallel, plasminogen was investigated in CSF from patients with Guillain-Barré syndrome (n = 15), multiple sclerosis (n = 19) and noninflammatory neurological diseases (n = 8). Results Endogenous rat plasminogen was detected in higher amounts in the CSF and urine of LPS-treated animals as compared to controls. In LPS-primed rats, circulating Alexa Fluor 488–labelled rat plasminogen was abundantly localized in the choroid plexus, CSF and urine. Plasminogen in human CSF was higher in Guillain-Barré syndrome (median = 1.28 ng/μl (interquartile range (IQR) = 0.66 to 1.59)) as compared to multiple sclerosis (median = 0.3 ng/μl (IQR = 0.16 to 0.61)) and to noninflammatory neurological diseases (median = 0.27 ng/μl (IQR = 0.18 to 0.35)). Conclusions Our findings demonstrate that plasminogen is transported from circulating blood into the CSF of rats via the choroid plexus during inflammation. Our data suggest that a similar mechanism may explain the high CSF concentrations of plasminogen detected in patients with inflammation-derived CSF barrier impairment. Electronic supplementary material The online version of this article (doi:10.1186/s12974-014-0154-y) contains supplementary material, which is available to authorized users.

Published
2014
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4. Plasmin on adherent cells: from microvesiculation to apoptosis.: Cell activation by plasmin: microvesiculation, apoptosis

Author

Laurent Plawinski, Denis Vivien, Eduardo Anglés-Cano, Didier Goux, Loïc Doeuvre, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre-Imagerie, Neurosciences, et Application aux Pathologies (CI-NAPS - UMR 6232), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Inserm, European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement [201024]., European Project: 201024,EC:FP7:HEALTH,FP7-HEALTH-2007-A,ARISE(2008), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)

Subjects
genetic structures, Plasmin, Cell, MESH: Cricetinae, MESH: Fibrinolysin, Biochemistry, Tissue plasminogen activator, Cell membrane, 0302 clinical medicine, MESH: Cricetulus, Cricetinae, MESH: Tissue Plasminogen Activator, MESH: Plasminogen, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Animals, Fibrinolysin, MESH: In Situ Nick-End Labeling, MESH: Blood Platelets, microparticles, 0303 health sciences, MESH: Kinetics, apoptosis, Life Sciences, Cell biology, medicine.anatomical_structure, MESH: Cell Survival, Tissue Plasminogen Activator, Cell activation, medicine.drug, Blood Platelets, Cell Survival, Blotting, Western, CHO Cells, MESH: Microscopy, Electron, Biology, Article, MESH: Cell Adhesion, 03 medical and health sciences, Cricetulus, MESH: CHO Cells, Cell Adhesion, In Situ Nick-End Labeling, medicine, Animals, Humans, MESH: Blotting, Western, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cell adhesion, Molecular Biology, 030304 developmental biology, MESH: Humans, electron microscopy, MESH: Apoptosis, Plasminogen, Cell Biology, Kinetics, Microscopy, Electron, membrane blebbing, Apoptosis, Plasminogen activator, 030217 neurology & neurosurgery
Abstract

International audience; Cell activation by stressors is characterized by a sequence of detectable phenotypic cell changes. A given stimulus, depending on its strength, induces modifications in the activity of membrane phospholipid transporters and calpains, which lead to phosphatidylserine exposure, membrane blebbing and the release of microparticles (nanoscale membrane vesicles). This vesiculation could be considered as a warning signal that may be followed, if the stimulus is maintained, by cell detachment-induced apoptosis. In the present study, plasminogen incubated with adherent cells is converted into plasmin by constitutively expressed tPA (tissue-type plasminogen activator) or uPA (urokinase-type plasminogen activator). Plasmin formed on the cell membrane then induces a unique response characterized by membrane blebbing and vesiculation. Hitherto unknown for plasmin, these membrane changes are similar to those induced by thrombin on platelets. If plasmin formation persists, matrix proteins are then degraded, cells lose their attachments and enter the apoptotic process, characterized by DNA fragmentation and specific ultrastructural features. Since other proteolytic or inflammatory stimuli may evoke similar responses in different types of adherent cells, the proposed experimental procedure can be used to distinguish activated adherent cells from cells entering the apoptotic process. Such a distinction is crucial for evaluating the effects of mediators, inhibitors and potential therapeutic agents.

Published
2010
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5. Fibrinolytic cross-talk: a new mechanism for plasmin formation

Author

Dejouvencel, Tiphaine, Doeuvre, Loïc, Lacroix, Romaric, Plawinski, Laurent, Dignat-George, Francoise, Lijnen, Henri Roger, Angles-Cano, Eduardo, Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de l'Endothelium, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre-Imagerie, Neurosciences, et Application aux Pathologies (CI-NAPS - UMR 6232), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Center for Molecular and Vascular Biology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Inserm European Community's Seventh Framework Programme (FP7/2007-2013) Excellentie financiering, KU Leuven Lower-Normandy Regional Council, European Project: 201024,EC:FP7:HEALTH,FP7-HEALTH-2007-A,ARISE(2008), Angles-Cano, Eduardo, and Affording Recovery In Stroke - ARISE - - EC:FP7:HEALTH2008-03-01 - 2013-08-31 - 201024 - VALID

Subjects
MESH: Signal Transduction, MESH: Receptor Cross-Talk, MESH: Antifibrinolytic Agents, urokinase, MESH: Fibrinolysin, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Extracellular Matrix, endothelial microparticles, MESH: Urokinase-Type Plasminogen Activator, MESH: Fibrinolysis, MESH: 6-Aminocaproic Acid, MESH: Plasminogen, MESH: Cell Communication, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Humans, MESH: Plasminogen Activators, lysine-binding site, MESH: Protein Processing, Post-Translational, platelets, plasminogen, monocytes, MESH: Cells, Cultured
Abstract

International audience; Fibrinolysis and pericellular proteolysis depend on molecular coassembly of plasminogen and its activator on cell, fibrin, or matrix surfaces. We report here the existence of a fibrinolytic cross-talk mechanism bypassing the requirement for their molecular coassembly on the same surface. First, we demonstrate that, despite impaired binding of Glu-plasminogen to the cell membrane by epsilon-aminocaproic acid (epsilon-ACA) or by a lysine-binding site-specific mAb, plasmin is unexpectedly formed by cell-associated urokinase (uPA). Second, we show that Glu-plasminogen bound to carboxy-terminal lysine residues in platelets, fibrin, or extracellular matrix components (fibronectin, laminin) is transformed into plasmin by uPA expressed on monocytes or endothelial cell-derived microparticles but not by tissue-type plasminogen activator (tPA) expressed on neurons. A 2-fold increase in plasmin formation was observed over activation on the same surface. Altogether, these data indicate that cellular uPA but not tPA expressed by distinct cells is specifically involved in the recognition of conformational changes and activation of Glu-plasminogen bound to other biologic surfaces via a lysine-dependent mechanism. This uPA-driven cross-talk mechanism generates plasmin in situ with a high efficiency, thus highlighting its potential physiologic relevance in fibrinolysis and matrix proteolysis induced by inflammatory cells or cell-derived microparticles.

Published
2010
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6. Plasmin on adherent cells: from microvesiculation to apoptosis

Author

Doeuvre, Loïc, Plawinski, Laurent, Goux, Didier, Vivien, Denis, Anglés-Cano, Eduardo, Angles-Cano, Eduardo, Affording Recovery In Stroke - ARISE - - EC:FP7:HEALTH2008-03-01 - 2013-08-31 - 201024 - VALID, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre-Imagerie, Neurosciences, et Application aux Pathologies (CI-NAPS - UMR 6232), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions Cellules Organismes Environnement (ICORE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Inserm, European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement [201024]., and European Project: 201024,EC:FP7:HEALTH,FP7-HEALTH-2007-A,ARISE(2008)

Subjects
microparticles, MESH: Humans, electron microscopy, MESH: Kinetics, MESH: Apoptosis, apoptosis, MESH: Cricetinae, Plasminogen, MESH: Microscopy, Electron, MESH: Fibrinolysin, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Cell Adhesion, membrane blebbing, MESH: Cell Survival, MESH: Cricetulus, MESH: CHO Cells, MESH: Tissue Plasminogen Activator, MESH: Plasminogen, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Blotting, Western, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: In Situ Nick-End Labeling, MESH: Blood Platelets
Abstract

International audience; Cell activation by stressors is characterized by a sequence of detectable phenotypic cell changes. A given stimulus, depending on its strength, induces modifications in the activity of membrane phospholipid transporters and calpains, which lead to phosphatidylserine exposure, membrane blebbing and the release of microparticles (nanoscale membrane vesicles). This vesiculation could be considered as a warning signal that may be followed, if the stimulus is maintained, by cell detachment-induced apoptosis. In the present study, plasminogen incubated with adherent cells is converted into plasmin by constitutively expressed tPA (tissue-type plasminogen activator) or uPA (urokinase-type plasminogen activator). Plasmin formed on the cell membrane then induces a unique response characterized by membrane blebbing and vesiculation. Hitherto unknown for plasmin, these membrane changes are similar to those induced by thrombin on platelets. If plasmin formation persists, matrix proteins are then degraded, cells lose their attachments and enter the apoptotic process, characterized by DNA fragmentation and specific ultrastructural features. Since other proteolytic or inflammatory stimuli may evoke similar responses in different types of adherent cells, the proposed experimental procedure can be used to distinguish activated adherent cells from cells entering the apoptotic process. Such a distinction is crucial for evaluating the effects of mediators, inhibitors and potential therapeutic agents.

Published
2010
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7. Elastolysis induces collagenolysis in a gingival lamina propria model

Author

Hillard Kaplan, William Hornebeck, Sébastien Barthelemy, Roselyne Garnotel, Anne Cozlin, Sandrine Lorimier, Franck Antonicelli, Matrice extracellulaire et régulations cellulaires (MERC), Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Laurent-Maquin, Dominique, Maquart, François-Xavier, Interfaces biomatériaux/tissus hôtes, and Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Pathology, Fibrillar Collagens, Cell Culture Techniques, Gingiva, Matrix metalloproteinase, Matrix (biology), Stromelysin 1, 0302 clinical medicine, MESH: Plasminogen, Receptor, Cells, Cultured, MESH: Middle Aged, biology, Chemistry, Reverse Transcriptase Polymerase Chain Reaction, MESH: Research Support, N, Tissue Inhibitor of Metalloproteinases, Middle Aged, Cell biology, MESH: Oligopeptides, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Matrix Metalloproteinase 3, Matrix Metalloproteinase 1, Oligopeptides, MESH: Cells, Cultured, Adult, MESH: Enzyme Activation, medicine.medical_specialty, Cell type, Blotting, Western, MESH: Elastin, Models, Biological, 03 medical and health sciences, medicine, MESH: Blotting, Western, MESH: Fibrillar Collagens, Humans, General Dentistry, MESH: Gingiva, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Periodontitis, MESH: Cell Culture Techniques, MESH: Humans, MESH: Models, Biological, MESH: Adult, Plasminogen, 030206 dentistry, Tissue inhibitor of metalloproteinase, Fibroblasts, medicine.disease, Elastin, Enzyme Activation, 030104 developmental biology, MESH: Fibroblasts, MESH: Interstitial Collagenase, biology.protein
Abstract

Elastin peptides were previously reported to increase MMP expression in several cell types. We found binding of these peptides to their receptors led to enhanced MMP-3 and MMP-1 expression, but not activation, in human gingival fibroblasts cultured on plastic dishes. We hypothesized that these peptides, in a more physiological environment, might additionally trigger an MMP-3/MMP-1 activation cascade, leading to matrix lysis, as occurs in periodontitis. To test this hypothesis, we used contracted and attached lattices as gingival lamina propria equivalents. In such 3D models, supplementation of elastin peptides and plasminogen triggered an MMP-3/MMP-1 activation cascade and significant down-regulation of TIMPs production, further leading to intense collagen degradation. We propose that elastolysis, as occurs in periodontitis, potentiates collagenolysis, thus promoting disease progression.

Published
2006

8. Plasminogen activation: a mediator of vascular smooth muscle cell apoptosis in atherosclerotic plaques

Author

Rossignol, Patrick, Luttun, Aernout, Martin-Ventura, Jose Luis, Lupu, Florea, Carmeliet, Peter, Collen, Désiré, Anglès-Cano, Eduardo, Lijnen, Henri Roger, Center for Molecular and Vascular Biology, Catholic University of Leuven ( KU Leuven ), Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Galilée, Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Inserm, Leducq Foundation, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Oklahoma Medical Research Foundation (OMRF), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH : Antiplasmin, MESH : Plasminogen Activator Inhibitor 1, MESH : Atherosclerosis, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH : Mice, Inbred C57BL, MESH: Mice, Knockout, MESH: Plasminogen Activator Inhibitor 1, MESH : Tunica Media, MESH: Atherosclerosis, MESH: Mice, Inbred C57BL, MESH: Antiplasmin, MESH: Plasminogen, MESH : Plasmin, MESH : Apolipoproteins E, MESH : Mice, MESH: Animals, genetically altered mice, MESH: Mice, MESH: Plasmin, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Apoptosis, apoptosis, MESH : Aorta, MESH: Aorta, MESH : Muscle, Smooth, Vascular, MESH: Muscle, Smooth, Vascular, MESH: Apolipoproteins E, MESH : Disease Models, Animal, MESH: Tunica Media, MESH : Plasminogen, cardiovascular system, plasminogen, MESH : Mice, Knockout, MESH : Animals, MESH: Disease Models, Animal, atherosclerosis, vascular smooth muscle cell, MESH : Apoptosis
Abstract

21 pages; International audience; BACKGROUND: Apoptosis of vascular cells is considered to be a major determinant of atherosclerotic plaque vulnerability and potential rupture. Plasmin can be generated in atherosclerotic plaques and recent in vitro data suggest that plasminogen activation may trigger vascular smooth muscle cell (VSMC) apoptosis. AIM: To determine whether plasminogen activation may induce aortic VSMC apoptosis ex vivo and in vivo. METHODS AND RESULTS: Mice with single or combined deficiencies of apolipoprotein E (ApoE) and plasminogen activator inhibitor-1 (PAI-1) were used. Ex vivo incubation with plasminogen of isolated aortic tunica media from PAI-1-deficient mice induced plasminogen activation and VSMC apoptosis, which was inhibited by alpha2-antiplasmin. In vivo, levels of plasmin, active caspase 3 and VSMC apoptotic index were significantly higher in atherosclerotic aortas from mice with combined ApoE and PAI-1 deficiencies than in those from littermates with single ApoE deficiency. A parallel decrease in VSMC density was observed. CONCLUSIONS: These data strongly suggest that plasminogen activation may contribute to VSMC apoptosis in atherosclerotic plaques.

Published
2006
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9. Plasminogen activation: a mediator of vascular smooth muscle cell apoptosis in atherosclerotic plaques.: Plasmin induces VSMC apoptosis in atherosclerosis

Author

Rossignol, Patrick, Luttun, Aernout, Martin-Ventura, Jose Luis, Lupu, Florea, Carmeliet, Peter, Collen, Désiré, Anglès-Cano, Eduardo, Lijnen, Henri Roger, Angles-Cano, Eduardo, Center for Molecular and Vascular Biology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation (OMRF), Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Inserm, Leducq Foundation

Subjects
MESH: Plasmin, MESH: Apoptosis, apoptosis, MESH: Aorta, MESH: Muscle, Smooth, Vascular, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Apolipoproteins E, MESH: Mice, Knockout, MESH: Plasminogen Activator Inhibitor 1, MESH: Atherosclerosis, MESH: Tunica Media, MESH: Mice, Inbred C57BL, MESH: Antiplasmin, MESH: Plasminogen, cardiovascular system, plasminogen, MESH: Animals, genetically altered mice, atherosclerosis, vascular smooth muscle cell, MESH: Disease Models, Animal, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice
Abstract

21 pages; International audience; BACKGROUND: Apoptosis of vascular cells is considered to be a major determinant of atherosclerotic plaque vulnerability and potential rupture. Plasmin can be generated in atherosclerotic plaques and recent in vitro data suggest that plasminogen activation may trigger vascular smooth muscle cell (VSMC) apoptosis. AIM: To determine whether plasminogen activation may induce aortic VSMC apoptosis ex vivo and in vivo. METHODS AND RESULTS: Mice with single or combined deficiencies of apolipoprotein E (ApoE) and plasminogen activator inhibitor-1 (PAI-1) were used. Ex vivo incubation with plasminogen of isolated aortic tunica media from PAI-1-deficient mice induced plasminogen activation and VSMC apoptosis, which was inhibited by alpha2-antiplasmin. In vivo, levels of plasmin, active caspase 3 and VSMC apoptotic index were significantly higher in atherosclerotic aortas from mice with combined ApoE and PAI-1 deficiencies than in those from littermates with single ApoE deficiency. A parallel decrease in VSMC density was observed. CONCLUSIONS: These data strongly suggest that plasminogen activation may contribute to VSMC apoptosis in atherosclerotic plaques.

Published
2006
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10. Tissue origin and extracellular matrix control neutral proteinase activity in human fibroblast three-dimensional cultures

Author

Sylvie Bouthors, Philippe Gillery, Dominique Laurent-Maquin, Sandrine Lorimier, William Hornebeck, Chantal Droulle, François-Xavier Maquart, François Chastang, Gérard Potron, Laboratoire de Biochimie (LB), Faculté de Médecine-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Recherche en Odontologie (LRO), Faculté de Chirurgie Dentaire de Rennes, Laboratoire Central d'Hématologie (LCH), Centre hospitalier Universitaire, Laurent-Maquin, Dominique, Université de Rennes - UFR d'Odontologie (UR Odontologie), and Université de Rennes (UR)-Université de Rennes (UR)

Subjects
Physiology, medicine.medical_treatment, Clinical Biochemistry, Gingiva, MESH: Research Support, Non-U.S. Gov't, Extracellular matrix, chemistry.chemical_compound, MESH: Tissue Plasminogen Activator, MESH: Plasminogen, MESH: Endopeptidases, MESH: Fibrin, Cells, Cultured, Skin, MESH: Middle Aged, biology, Middle Aged, Extracellular Matrix, medicine.anatomical_structure, Biochemistry, Tissue Plasminogen Activator, [SDV.IB]Life Sciences [q-bio]/Bioengineering, MESH: Cells, Cultured, Adult, MESH: Microscopy, Electron, Scanning, MESH: Extracellular Matrix, Fibrin, Dermis, MESH: Skin, Fibrinolysis, Endopeptidases, medicine, Humans, Fibroblast, MESH: Gingiva, [SDV.IB] Life Sciences [q-bio]/Bioengineering, MESH: End, MESH: Humans, Plasminogen, MESH: Adult, Cell Biology, Fibroblasts, Molecular biology, Fibronectin, chemistry, MESH: Fibroblasts, biology.protein, Microscopy, Electron, Scanning, PMSF, Wound healing
Abstract

Remodeling of the extracellular matrix by fibroblasts is an important step in the process of wound healing and tissue repair. We compared the behavior of fibroblasts from two different tissues, dermis and gingiva, in three-dimensional lattices made of two different extracellular matrix macromolecules, collagen and fibrin. Cells were grown in monolayer cultures from normal skin or gingiva and seeded in three-dimensional lattices made of either collagen of fibrin. Photonic and scanning electron microscopy did not reveal any morphological differences between the two types of fibroblasts in both sets of lattices. Both types of fibroblasts retracted collagen lattices similarly and caused only a slight degradation of the collagen substratum. By contrast, when seeded in fibrin lattices, gingival fibroblasts completely digested their substratum in less than 8 days, whereas only a slight fibrin degradation was observed with dermal fibroblasts. The ability of gingival but not dermal fibroblasts to express high levels of tissue plasminogen activators (tPA) when cultured in fibrin lattices was assessed on an immunological basis. Also, deprivation of plasminogen-contaminating fibrinogen preparations or use of tPA inhibitors markedly inhibited both fibrinolysis and retraction rates of fibrin lattices by gingival fibroblasts. Casein-zymography confirmed the intense proteolytic activity induced by fibrin in gingival fibroblasts. It was inhibited by aprotinin and phenyl methylsulfonyl fluoride (PMSF), two non-specific inhibitors of serine proteinases, and by epsilon-amino-caproic acid (epsilon ACA), an inhibitor of plasminogen activators. Monolayer cultures exhibited only trace amounts of caseinolytic activity. Our results demonstrate that the expression of proteinases by fibroblasts is dependent not only on their tissue origin but also on the surrounding extracellular matrix. The intense fibrinolytic activity of gingival fibroblasts in fibrin lattices may explain partially the high rate of healing clinically observed in gingiva.

Published
1996
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